Cephalon, Inc.

American Home Products Corporation

James L Diebold

Robert L Hudkins

Diane E Gingrich

Theodore L Underiner

Bruce D Dorsey

Koc-Kan Ho

Sankar Chatterjee

Allison L Zulli

Michael W Winkley

James C Kauer

Mohamed A Iqbal

Robert Siman

Gregory J Wells

Henry Joseph Breslin

Meier E Freed

Gregory R Ott

Rabindranath Tripathy

Ming Tao

Craig A Zificsak

Nadine C Becknell

Karen L Milkiewicz

Eugen F Mesaros

Joseph Lisko

Jay P Theroff

Tho V Thieu

Tao Guo

Derek D Dunn

Keith S Learn

Ernest Knight, Jr

Benjamin J Dugan

Gulzar Ahmed

Dandu R Reddy

Matthew A Curry

Rong-qiang Liu

Jason Burke

Daming Feng

Kurt A Josef

Reddeppa Reddy Dandu

Greg A Hostetler

Linda Weinberg

Peter D Brown

Babu G Sundar

Bruce A Ruggeri

Jason C Wagner

Reddeppareddy Dandu

Ming You

Rachael Hunter

Sheila J Miknyoczki

Bruce Dorsey

Adolph Bohnstedt

Karen Milkiewicz

Jonathan Parrish

Joseph G Lisko

Rong-Qiang Liu

The present invention is directed to novel multicyclic molecules that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of PARP, VEGFR2, and MLK3 enzymes, including, for example, neurodegenerative diseases, inflammation, ischemia, and cancer.

Multicyclic compounds and the use thereof

The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R, R, R, R, R, A, A, A, A, and A, are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-MET inhibitors

The present invention provides a compound of formula I or a salt form thereof, wherein Q, Q, Q, and Qare as defined herein. The compound of formula I has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

Pyrrolotriazines as ALK and JAK2 inhibitors

The present invention relates generally to selected fused pyrrolocarbazoles, including pharmaceutical compositions thereof and methods of treating diseases therewith. The present invention is also directed to intermediates and processes for making these fused pyrrolocarbazoles.

Fused pyrrolocarbazoles

The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R, R, R, R, R, A, A, A, A, and A, are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders. 

Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met inhibitors

Disclosed herein are inhibitors of the multicatalytic protease enzyme which are represented by the general formula: ##STR1## Constituent members and preferred constituent members are disclosed herein. Methodologies for making and using the disclosed compounds are also set forth herein.

Multicatalytic protease inhibitors

Disclosed in this patent document are synthetic, biologically active molecules referred to as fused pyrrolo�2,3-c!carbazole-6-ones. These molecules are represented by the following general formulae: ##STR1## Methods for making and using the fused pyrrolo�2,3-c!carbazole-6-ones are also disclosed.

Fused pyrrolo�2,3-C! carbazole-6-ones

Disclosed in this patent document are synthetic, biologically active molecules referred to as fused pyrrolo[2,3-c]carbazole-6-ones. These molecules are represented by the following general formulae: ##STR1## Methods for making and using the fused pyrrolo[2,3-c]carbazole-6-ones are also disclosed.

Fused pyrrolo[2,3-c]carbazole-6-ones

Disclosed herein are inbibitors of the multicatalytic protease enzyme which are represented by the general formula: ##STR1## Constituent members and preferred constituent members are disclosed herein. Methodologies for making and using the disclosed compounds are also set forth herein.

Disclosed herein are novel 1,2,3,4,5,6-hexahydro[1,3,6]triazocino[1,2-a]benzimidazole of Formulas I and II: ##STR1## wherein R.sup.1 may be phenyl, m- or p-nitrophenyl, m- or p-methylsulfonylaminophenyl, napthtyl, naphthyl mono-substituted by nitro or methylsulfonylamino, benzofurazanyl, 2-pyrimidinyl, 2- or 4-pyridinyl, 2- or 4-naphthyridinyl, pyrazinyl, isoquinolinyl, or quinolinyl;

2,3,4,5-tetrahyd

Disclosed herein are novel 1,4-substituted-2,3,5,6-tetrahydro[1,3,6]triazocino[1,2-a]benzimidazole of Formulas I and II: ##STR1## wherein R.sup.1 may be phenyl, m- or p-nitrophenyl, m- or p-methylsulfonylaminophenyl, naphthyl, naphthyl mono-substituted by nitro or methylsulfonylamino, benzofurazanyl, 2-pyrimidinyl, 2- or 4-pyridinyl, 2- or 4-naphthyridinyl, pyrazinyl, isoquinolinyl, or quinolinyl; R.sup.2 may be hydrogen; C.sub.1 -C.sub.8 alkyl; C.sub.1 -C.sub.4 alkylphenyl or C.sub.1 -C.sub.4 alkyl-substituted-phenyl, in which phenyl may have one to three substituents selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, fluorine, chlorine or bromine; phenyl or substituted-phenyl in which the phenyl substituents are the same as for c.sub.1 -C.sub.4 alkyl-substituted-phenyl; 2- or 4-pyrimidinyl; pyrazinyl; imidazolyl; C.sub.1 -C.sub.4 alkanoyl; halo or dihalo-(C.sub.1 -C.sub.4)alkanoyl, in which halo is fluoro or chloro; benzoyl or benzoyl substituted on the phenyl ring by one or two C.sub.1 -C.sub.4 alkyl groups; C.sub.1 -C.sub.4 alkanoyloxy; C.sub.1 -C.sub.4 alkylamino(C.sub.1 -C.sub.4)alkanoyl; C.sub.1 -C.sub.4 alkyloxycarbonyl; C.sub.1 -C.sub.4 alkylaminocarbonyl; phenylaminocarbonyl in which phenyl may have one to three C.sub.1 -C.sub.4 alkyl groups; phenyloxy or naphthyloxy(C.sub.1 -C.sub.4)alkyl in which the phenyl or naphthyl ring may be substituted by one to three C.sub.1 - C.sub.4 alkyl groups; C.sub.1 -C.sub.4 alkylsulfonyl; N-(C.sub.1 -C.sub.4) alkyl- or N-(C.sub.1 -C.sub.4) dialkylcarboxamido(C.sub.1 -C.sub.4)alkyl; N-phenyl or substituted phenyl-carboxamido(C.sub.1 -C.sub.4)alkyl in which phenyl may be substituted as above for C.sub.1 -C.sub.4 alkyl-substituted phenyl; cyano; amidino in which each N atom is substituted by a C.sub.1 -C.sub.4 alkyl group; and C.sub.1 -C.sub.4 alkylguanidino; and R.sup.3 and R.sup.4 are, independently, selected from hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, fluorine and chlorine, or acid addition salts thereof. Compounds of formulas I and II having certain values of R.sup.2 are antiarrhythmic or antiischaemic agents. The remaining values of R.sup.2 provide intermediate compounds of formulas I and II. Also disclosed herein a novel tetrahydro-3-substituted-7-substituted-1H-[1,2,5]triazepino[1,2-a][1,2,4]b enzotriazines, wherein the 7 substituent may be --SMe, .dbd.S, .dbd.O, Cl or Br and the 3 substituent is the same as R.sup.2 in formulas I and II above. These componds also serve as intermediates for the production of the antiarrhythmic agents of formula II above.

1,2,3,4,5,6-hexahydro[1,3,6]triazocino[1,1-a]benzimidazoles

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Eagleville, PA, United States of America

James L Diebold